Wardle T D, Hall L, Turnberg L A
Epithelial Membrane Research Centre, University of Manchester, Hope Hospital, Salford.
Gut. 1996 Mar;38(3):355-61. doi: 10.1136/gut.38.3.355.
Inflammatory mediators have been implicated in the pathophysiology of ulcerative colitis. They may stimulate intestinal secretion and contribute to the production of diarrhoea. Platelet activating factor (PAF) may be responsible for a high proportion of this secretory response. Biopsy specimens from inflamed and quiescent mucosa of patients with ulcerative colitis and normal human colonic mucosa were cultured or co-cultured. The release of PAF, prostaglandin E2, and leukotriene D4 into the culture medium was measured and the ability of this culture medium, from inflamed and normal tissues, to influence secretion in rat colonic mucosa was assessed. PAF was liberated by inflamed tissue. Its release from quiescent but not normal tissue was stimulated by medium in which inflamed mucosal biopsy tissues had been cultured and by exogenous bradykinin and 5-hydroxytryptamine, but not by histamine. PAF stimulated eicosanoid production. The rise in short circuit current produced in vitro by inflamed tissue culture medium was inhibited by the PAF receptor antagonist (CV 6209) (46%) (32.4 (2.9) v 17.5 (1.19) muA.cm-2, p < 0.005) and further by combined cyclooxygenase and lipoxygenase inhibition (indomethacin plus ICI 207968) (58%) (32.4 (2.9) v 13.6 (1.9) muA.cm-2, p < 0.005). Mepacrine and hydrocortisone attenuated considerably the electrical response evoked by medium from inflamed mucosa to a similar extent (32.4 (2.9) v 6.3 (1.2) v 5.1 (0.9) muA.cm-2, p < 0.001). These data suggest that PAF accounted for 46% of the culture medium secretory effect. Thus, any attempt to block its release in patients with ulcerative colitis may have only a partial effect on their symptoms.
炎症介质与溃疡性结肠炎的病理生理学有关。它们可能刺激肠道分泌并导致腹泻。血小板活化因子（PAF）可能是这种分泌反应的很大一部分原因。对溃疡性结肠炎患者的炎症和静止黏膜以及正常人类结肠黏膜的活检标本进行培养或共培养。测量PAF、前列腺素E2和白三烯D4释放到培养基中的量，并评估来自炎症组织和正常组织的这种培养基影响大鼠结肠黏膜分泌的能力。炎症组织释放PAF。静止但非正常组织释放PAF受到炎症黏膜活检组织培养过的培养基以及外源性缓激肽和5-羟色胺的刺激，但不受组胺刺激。PAF刺激类花生酸的产生。炎症组织培养基在体外产生的短路电流升高受到PAF受体拮抗剂（CV 6209）的抑制（46%）（32.4（2.9）对17.5（1.19）μA·cm-2，p<0.005），联合环氧化酶和脂氧化酶抑制（吲哚美辛加ICI 207968）进一步抑制（58%）（32.4（2.9）对13.6（1.9）μA·cm-2，p<0.005）。氯喹和氢化可的松在很大程度上减弱了炎症黏膜培养基引起的电反应（32.4（2.9）对6.3（1.2）对5.1（0.9）μA·cm-2，p<0.001）。这些数据表明PAF占培养基分泌作用的46%。因此，任何试图阻断溃疡性结肠炎患者PAF释放的尝试可能只会对其症状产生部分影响。
